| 1. |
- Ares-Blanco, Sara, et al.
(author)
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Primary care indicators for disease burden, monitoring and surveillance of COVID-19 in 31 European countries: Eurodata Study
- 2024
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In: EUROPEAN JOURNAL OF PUBLIC HEALTH. - 1101-1262 .- 1464-360X.
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Journal article (peer-reviewed)abstract
- Background During the COVID-19 pandemic, the majority of patients received ambulatory treatment, highlighting the importance of primary health care (PHC). However, there is limited knowledge regarding PHC workload in Europe during this period. The utilization of COVID-19 PHC indicators could facilitate the efficient monitoring and coordination of the pandemic response. The objective of this study is to describe PHC indicators for disease surveillance and monitoring of COVID-19's impact in Europe.Methods Descriptive, cross-sectional study employing data obtained through a semi-structured ad hoc questionnaire, which was collectively agreed upon by all participants. The study encompasses PHC settings in 31 European countries from March 2020 to August 2021. Key-informants from each country answered the questionnaire. Main outcome: the identification of any indicator used to describe PHC COVID-19 activity.Results Out of the 31 countries surveyed, data on PHC information were obtained from 14. The principal indicators were: total number of cases within PHC (Belarus, Cyprus, Italy, Romania and Spain), number of follow-up cases (Croatia, Cyprus, Finland, Spain and Turkey), GP's COVID-19 tests referrals (Poland), proportion of COVID-19 cases among respiratory illnesses consultations (Norway and France), sick leaves issued by GPs (Romania and Spain) and examination and complementary tests (Cyprus). All COVID-19 cases were attended in PHC in Belarus and Italy.Conclusions The COVID-19 pandemic exposes a crucial deficiency in preparedness for infectious diseases in European health systems highlighting the inconsistent recording of indicators within PHC organizations. PHC standardized indicators and public data accessibility are urgently needed, conforming the foundation for an effective European-level health services response framework against future pandemics.
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| 2. |
- Aczel, Balazs, et al.
(author)
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Consensus-based guidance for conducting and reporting multi-analyst studies
- 2021
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In: eLIFE. - : eLife Sciences Publications. - 2050-084X. ; 10
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Journal article (peer-reviewed)abstract
- Any large dataset can be analyzed in a number of ways, and it is possible that the use of different analysis strategies will lead to different results and conclusions. One way to assess whether the results obtained depend on the analysis strategy chosen is to employ multiple analysts and leave each of them free to follow their own approach. Here, we present consensus-based guidance for conducting and reporting such multi-analyst studies, and we discuss how broader adoption of the multi-analyst approach has the potential to strengthen the robustness of results and conclusions obtained from analyses of datasets in basic and applied research.
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| 3. |
- Boeing, Heiner, et al.
(author)
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Intake of fruits and vegetables and risk of cancer of the upper aero-digestive tract: the prospective EPIC-study
- 2006
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In: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 17:7, s. 957-969
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Journal article (peer-reviewed)abstract
- Epidemiologic studies suggest that a high intake of fruits and vegetables is associated with decreased risk of cancers of the upper aero-digestive tract. We studied data from 345,904 subjects of the prospective European Investigation into Cancer and Nutrition (EPIC) recruited in seven European countries, who had completed a dietary questionnaire in 1992-1998. During 2,182,560 person years of observation 352 histologically verified incident squamous cell cancer (SCC) cases (255 males; 97 females) of the oral cavity, pharynx, larynx, and esophagus were identified. Linear and restricted cubic spline Cox regressions were fitted on variables of intake of fruits and vegetables and adjusted for potential confounders. We observed a significant inverse association with combined total fruits and vegetables intake (estimated relative risk (RR) = 0.91; 95% confidence interval (95% CI) 0.83-1.00 per 80 g/d of consumption), and nearly significant inverse associations in separate analyses with total fruits and total vegetables intake (RR: 0.97 (95% CI: 0.92-1.02) and RR = 0.89 (95% CI: 0.78-1.02) per 40 g/d of consumption). Overall, vegetable subgroups were not related to risk with the exception of intake of root vegetables in men. Restricted cubic spline regression did not improve the linear model fits except for total fruits and vegetables and total fruits with a significant decrease in risk at low intake levels (< 120 g/d) for fruits. Dietary recommendations should consider the potential benefit of increasing fruits and vegetables consumption for reducing the risk of cancers of the upper aero-digestive tract, particularly at low intake.
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| 4. |
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| 5. |
- Eguiluz-Gracia, Ibon, et al.
(author)
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The need for clean air : The way air pollution and climate change affect allergic rhinitis and asthma
- 2020
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In: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538. ; 75:9, s. 2170-2184
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Research review (peer-reviewed)abstract
- Air pollution and climate change have a significant impact on human health and well-being and contribute to the onset and aggravation of allergic rhinitis and asthma among other chronic respiratory diseases. In Westernized countries, households have experienced a process of increasing insulation and individuals tend to spend most of their time indoors. These sequelae implicate a high exposure to indoor allergens (house dust mites, pets, molds, etc), tobacco smoke, and other pollutants, which have an impact on respiratory health. Outdoor air pollution derived from traffic and other human activities not only has a direct negative effect on human health but also enhances the allergenicity of some plants and contributes to global warming. Climate change modifies the availability and distribution of plant- and fungal-derived allergens and increases the frequency of extreme climate events. This review summarizes the effects of indoor air pollution, outdoor air pollution, and subsequent climate change on asthma and allergic rhinitis in children and adults and addresses the policy adjustments and lifestyle changes required to mitigate their deleterious effects.
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| 6. |
- Ford, Alex T., et al.
(author)
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The Role of Behavioral Ecotoxicology in Environmental Protection
- 2021
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In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 55:9, s. 5620-5628
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Journal article (peer-reviewed)abstract
- For decades, we have known that chemicals affect human and wildlife behavior. Moreover, due to recent technological and computational advances, scientists are now increasingly aware that a wide variety of contaminants and other environmental stressors adversely affect organismal behavior and subsequent ecological outcomes in terrestrial and aquatic ecosystems. There is also a groundswell of concern that regulatory ecotoxicology does not adequately consider behavior, primarily due to a lack of standardized toxicity methods. This has, in turn, led to the exclusion of many behavioral ecotoxicology studies from chemical risk assessments. To improve understanding of the challenges and opportunities for behavioral ecotoxicology within regulatory toxicology/risk assessment, a unique workshop with international representatives from the fields of behavioral ecology, ecotoxicology, regulatory (eco)toxicology, neurotoxicology, test standardization, and risk assessment resulted in the formation of consensus perspectives and recommendations, which promise to serve as a roadmap to advance interfaces among the basic and translational sciences, and regulatory practices.
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| 7. |
- Frampton, Matthew, et al.
(author)
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Variation at 3p24.1 and 6q23.3 influences the risk of Hodgkin's lymphoma
- 2013
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4
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Journal article (peer-reviewed)abstract
- In addition to HLA, recent genome-wide association studies (GWASs) of Hodgkin's lymphoma (HL) have identified susceptibility loci for HL at 2p16.1, 8q24.21 and 10p14. In this study, we perform a GWAS meta-analysis with published GWAS (totalling 1,465 cases and 6,417 controls of European background), and follow-up the most significant association signals in 2,024 cases and 1,853 controls. A combined analysis identifies new HL susceptibility loci mapping to 3p24.1 (rs3806624; P = 1.14 x 10(-12), odds ratio (OR) = 1.26) and 6q23.3 (rs7745098; P = 3.42 x 10(-9), OR = 1.21). rs3806624 localizes 5' to the EOMES (eomesodermin) gene within a p53 response element affecting p53 binding. rs7745098 maps intergenic to HBS1L and MYB, a region previously associated with haematopoiesis. These findings provide further insight into the genetic and biological basis of inherited susceptibility to HL.
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| 8. |
- Frischknecht, Ulrich, et al.
(author)
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Screening auf problematischen Alkoholkonsum – Erhebung zur Umsetzung der S3-Leitlinienempfehlungen in der transdisziplinären Versorgung einer Modellregion : [Screening for Problematic Alcohol Consumption – A Survey on Guideline Implementation in Transdisciplinary Health Care of a Model Region]
- 2022
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In: Das Gesundheitswesen. - : Georg Thieme Verlag KG. - 0941-3790 .- 1439-4421. ; 84:01, s. 43-51
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Journal article (peer-reviewed)abstract
- Aim Recording the frequency of screenings for problematic alcohol consumption by professionals involved in the health care of respective patients. The German S3-guideline screening, diagnosis and treatment of alcohol-related disorders recommends the use of questionnaire-based screenings for all patients in all settings.Methods Cross-sectional survey on screening frequency among general practitioners, gynecologists, psychiatrists, child- and adolescent therapists, psychotherapists, social workers and midwives. Logistic regression was used to explore how healthcare professionals' attributes were associated with the implementation of screenings.Results With response rates of about 20%, health care professionals reported using screening instruments for an average of 6.9% of all patients during the previous four weeks. Most of the time, custom-made questions were used instead of the recommended instruments (AUDIT, AUDIT-C). Higher screening rates were reported for patients with newly diagnosed hypertension (21.2%), alcohol-related disorders (43.3%) and mental disorders (39.3%). Knowledge of the guideline was associated with implementation of screenings (OR=4.67; 95% KI 1.94-11.25, p<0.001).Conclusions Comprehensive screening for problematic alcohol use with questionnaire-based instruments in accordance with guidelines is far from being routinely implemented in the studied health care settings. Measures to increase the knowledge of the guidelines are necessary in order to increase the frequency of alcohol screening in health care.
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| 9. |
- Griessbach, Sabine, et al.
(author)
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Aerosol and cloud top height information of Envisat MIPAS measurements
- 2020
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In: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 13:3, s. 1243-1271
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Journal article (peer-reviewed)abstract
- Infrared limb emission instruments have a long history in measuring clouds and aerosol. In particular, the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) instrument aboard ESA's Envisat provides 10 years of altitude-resolved global measurements. Previous studies found systematic overestimations and underestimations of cloud top heights for cirrus and polar stratospheric clouds. To assess the cloud top height information and to characterise its uncertainty for the MIPAS instrument we performed simulations for ice clouds, volcanic ash, and sulfate aerosol. From the simulation results we found that in addition to the known effects of the field-of-view that can lead to a cloud top height overestimation, and broken cloud conditions that can lead to underestimation, the cloud extinction also plays an important role. While for optically thick clouds the possible cloud top height overestimation for MIPAS reaches up to 1.6 km due to the field-of-view, for optically thin clouds and aerosol the systematic underestimation reaches 5.1 km. For the detection sensitivity and the degree of underestimation of the MIPAS measurements, the cloud layer thickness also plays a role; 1 km thick clouds are detectable down to extinctions of 5 x 10(-4) km(-1) and 6 km thick clouds are detectable down to extinctions of 1 x 10(-4) km(-1), where the largest underestimations of the cloud top height occur for the optically thinnest clouds with a vertical extent of 6 km. The relation between extinction coefficient, cloud top height estimate, and layer thickness is confirmed by a comparison of MIPAS cloud top heights of the volcanic sulfate aerosol from the Nabro eruption in 2011 with space- and ground-based lidar measurements and twilight measurements between June 2011 and February 2012. For plumes up to 2 months old, where the extinction was between 1 x 10(-4) and 7 x 10(-4) km(-1) and the layer thickness mostly below 4 km, we found for MIPAS an average underestimation of 1.1 km. In the aged plume with extinctions down to 5 x 10(-5) km(-1) and layer thicknesses of up to 9.5 km, the underestimation was higher, reaching up to 7.2 km. The dependency of the cloud top height overestimations or underestimations on the extinction coefficient can explain seemingly contradictory results of previous studies. In spite of the relatively large uncertainty range of the cloud top height, the comparison of the detection sensitivity towards sulfate aerosol between MIPAS and a suite of widely used UV/VIS limb and IR nadir satellite aerosol measurements shows that MIPAS provides complementary information in terms of detection sensitivity.
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| 10. |
- Guisado-Clavero, Marina, et al.
(author)
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The role of primary health care in long-term care facilities during the COVID-19 pandemic in 30 European countries : A retrospective descriptive study (Eurodata study)
- 2023
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In: Primary Health Care Research and Development. - 1463-4236. ; 24
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Journal article (peer-reviewed)abstract
- Background and aim: Primary health care (PHC) supported long-term care facilities (LTCFs) in attending COVID-19 patients. The aim of this study is to describe the role of PHC in LTCFs in Europe during the early phase of the pandemic. Methods: Retrospective descriptive study from 30 European countries using data from September 2020 collected with an ad hoc semi-structured questionnaire. Related variables are SARS-CoV-2 testing, contact tracing, follow-up, additional testing, and patient care. Results: Twenty-six out of the 30 European countries had PHC involvement in LTCFs during the COVID-19 pandemic. PHC participated in initial medical care in 22 countries, while, in 15, PHC was responsible for SARS-CoV-2 test along with other institutions. Supervision of individuals in isolation was carried out mostly by LTCF staff, but physical examination or symptom's follow-up was performed mainly by PHC. Conclusion: PHC has participated in COVID-19 pandemic assistance in LTCFs in coordination with LTCF staff, public health officers, and hospitals.
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| 11. |
- Hartkopf, Andreas D., et al.
(author)
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Disseminated tumour cells from the bone marrow of early breast cancer patients : Results from an international pooled analysis
- 2021
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 154, s. 128-137
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Journal article (peer-reviewed)abstract
- Purpose: Presence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC. Experimental design: Individual patient data were collected from 11 centres. Patients with EBC and available follow-up data in whom BM sampling was performed at the time of primary diagnosis before receiving any anticancer treatment were eligible. DTCs were identified by antibody staining against epithelial cytokeratins. Multivariate Cox regression was used to compare the survival of DTC-positive versus DTC-negative patients. Results: In total, 10,307 patients were included. Of these, 2814 (27.3%) were DTC-positive. DTC detection was associated with higher tumour grade, larger tumour size, nodal positivity, oestrogen receptor and progesterone receptor negativity, and HER2 positivity (all p < 0.001). Multivariate analyses showed that DTC detection was an independent prognostic marker for overall survival, disease-free survival and distant disease-free survival with hazard ratios (HR) and 95% confidence intervals (CI) of 1.23 (95% CI: 1.06–1.43, p = 0.006), 1.30 (95% CI: 1.12–1.52, p < 0.001) and 1.30 (95% CI: 1.08–1.56, p = 0.006), respectively. There was no association between locoregional relapse-free survival and DTC detection (HR 1.21; 95% CI 0.68–2.16; p = 0.512). Conclusions: DTCs in the BM represent an independent prognostic marker in patients with EBC. The heterogeneous metastasis-initiating potential of DTCs is consistent with the concept of cancer dormancy.
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| 12. |
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| 13. |
- Hoffmann, Mikael, et al.
(author)
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Guiding principles for the use of knowledge bases and real-world data in clinical decision support systems : report by an international expert workshop at Karolinska Institutet
- 2020
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In: Expert Review of Clinical Pharmacology. - : Taylor & Francis. - 1751-2433 .- 1751-2441. ; 13:9, s. 925-934
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Journal article (peer-reviewed)abstract
- Introduction Technical and logical breakthroughs have provided new opportunities in medicine to use knowledge bases and large-scale clinical data (real-world) at point-of-care as part of a learning healthcare system to diminish the knowledge-practice gap. Areas covered The article is based on presentations, discussions and recommendations from an international scientific workshop. Value, research needs and funding avenues of knowledge bases and access to real-world data as well as transparency and incorporation of patient perspectives are discussed. Expert opinion Evidence-based, publicly funded, well-structured and curated knowledge bases are of global importance. They ought to be considered as a public responsibility requiring transparency and handling of conflicts of interest. Information has to be made accessible for clinical decision support systems (CDSS) for healthcare staff and patients. Access to rich and real-world data is essential for a learning health care ecosystem and can be augmented by data on patient-reported outcomes and preferences. This field can progress by the establishment of an international policy group for developing a best practice guideline on the development, maintenance, governance, evaluation principles and financing of open-source knowledge bases and handling of real-world data.
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| 14. |
- Hoffmann, Sabine, et al.
(author)
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A Research Agenda for the Future of Urban Water Management : Exploring the Potential of Nongrid, Small-Grid, and Hybrid Solutions
- 2020
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In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 54:9, s. 5312-5322
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Research review (peer-reviewed)abstract
- Recent developments in high- and middle-income countries have exhibited a shift from conventional urban water systems to alternative solutions that are more diverse in source separation, decentralization, and modularization. These solutions include nongrid, small-grid, and hybrid systems to address such pressing global challenges as climate change, eutrophication, and rapid urbanization. They close loops, recover valuable resources, and adapt quickly to changing boundary conditions such as population size. Moving to such alternative solutions requires both technical and social innovations to coevolve over time into integrated socio-technical urban water systems. Current implementations of alternative systems in high- and middle-income countries are promising, but they also underline the need for research questions to be addressed from technical, social, and transformative perspectives. Future research should pursue a transdisciplinary research approach to generating evidence through socio-technical "lighthouse" projects that apply alternative urban water systems at scale. Such research should leverage experiences from these projects in diverse socio-economic contexts, identify their potentials and limitations from an integrated perspective, and share their successes and failures across the urban water sector.
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| 15. |
- Hudson, Lawrence N, et al.
(author)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Journal article (peer-reviewed)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 16. |
- Kowal-Bielecka, Otylia, et al.
(author)
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Update of EULAR recommendations for the treatment of systemic sclerosis
- 2017
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76, s. 1327-1339
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Journal article (peer-reviewed)abstract
- The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.
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| 17. |
- Pereira, Manuel P, et al.
(author)
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Chronic Nodular Prurigo : A European Cross-sectional Study of Patient Perspectives on Therapeutic Goals and Satisfaction
- 2021
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In: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 1651-2057. ; 101
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Journal article (peer-reviewed)abstract
- Chronic nodular prurigo is characterized by recalcitrant itch. Patient perspectives on therapeutic goals, satisfaction with therapy and efficacy of therapeutic regimens for this condition are unknown. This questionnaire study examined these issues in 406 patients with chronic nodular prurigo from 15 European dermatological centres. Improvements in itch, skin lesions and sleep were the most important goals. Emollients, topical corticosteroids and antihistamines were the most frequently used treatments, while a minority of patients were prescribed potent medications, such as systemic immunosuppressants and gabapentinoids. Most patients were not satisfied with their previous therapy (56.8%), while 9.8% did not receive any therapy despite having active disease. A substantial number of respondents (28.7%) considered none of the therapeutic options effective. Although chronic nodular prurigo is a severe disease, most patients were not treated with potent systemic drugs, which may contribute to the high levels of dissatisfaction and disbelief in available therapies. Specific guidelines for chronic nodular prurigo and the development of novel therapies are necessary to improve care.
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| 18. |
- Schulte, Bernd, et al.
(author)
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Tailored interventions to support the implementation of the German national guideline on screening, diagnosis and treatment of alcohol- related disorders : a project protocol
- 2019
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In: SUCHT. - : Hogrefe Publishing Group. - 0939-5911 .- 1664-2856. ; 65:6, s. 373-381
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Journal article (peer-reviewed)abstract
- Background: The German Guideline on Screening, Diagnosis and Treatment of Alcohol Use Disorders aims to increase the uptake of evidence-based interventions for the early identification, diagnosis, prevention and treatment of alcohol-related disorders in relevant healthcare settings. To date, dissemination has not been accompanied by a guideline implementation strategy. The aim of this study is to develop tailored guideline implementation strategies and to field-test these in relevant medical and psycho-social settings in the city of Bremen, Germany. Methods: The study will conduct an impact and needs assessment of healthcare provision for alcohol use orders in Bremen, drawing on a range of secondary and primary data to: evaluate existing healthcare services; model the potential impact of improved care on public health outcomes; and identify potential barriers and facilitators to implementing evidence-based guidelines. Community advisory boards will be established for the selection of single-component or multi-faceted guideline implementation strategies. The tailoring approach considers guideline, provider and organizational factors shaping implementation. In field tests quality outcome indicators of the delivery of evidence-based interventions will be evaluated accompanied by a process evaluation to examine patient, provider and organizational factors. Outlook: This project will support the translation of guideline recommendations for the identification, prevention and treatment of AUD in routine practice and therefore contributes to the reduction of alcohol-related burden in Germany. The project is running since October 2017 and will provide its main outcomes by end of 2020. Project results will be published in scientific journals and presented at national and international conferences.
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| 19. |
- Thomsen, Hauke, et al.
(author)
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Evidence of Inbreeding in Hodgkin Lymphoma
- 2016
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:4
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWASs) have identified several, mainly co-dominantly acting, single-nucleotide polymorphisms (SNPs) associated with Hodgkin lymphoma (HL). We searched for recessively acting disease loci by performing an analysis of runs of homozygosity (ROH) based on windows of homozygous SNP-blocks and by calculating genomic inbreeding coefficients on a SNP-wise basis. We used data from a previous GWAS with 906 cases and 1217 controls from a population with a long history of no matings between relatives. Ten recurrent ROHs were identified among 25 055 ROHs across all individuals but their association with HL was not genome-wide significant. All recurrent ROHs showed significant evidence for natural selection. As a novel finding genomic inbreeding among cases was significantly higher than among controls (P = 2.11*10-14) even after correcting for covariates. Higher inbreeding among the cases was mainly based on a group of individuals with a higher average length of ROHs per person. This result suggests a correlation of higher levels of inbreeding with higher cancer incidence and might reflect the existence of recessive alleles causing HL. Genomic inbreeding may result in a higher expression of deleterious recessive genes within a population.
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| 20. |
- Uhlmann, Eric, L., et al.
(author)
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Subjective Evidence Evaluation Survey For Multi-Analyst Studies
- 2024
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Other publication (other academic/artistic)abstract
- Multi-analyst studies explore how well an empirical claim withstands plausible alternative analyses of the same data set by multiple, independent analysis teams. Conclusions from these studies typically rely on a single outcome metric (e.g., effect size) provided by each analysis team. Although informative about the range of plausible effects in a data set, a single effect size from each team does not provide a complete, nuanced understanding of how analysis choices are related to the outcome. We used the Delphi consensus technique with input from 37 experts to develop an 18-item Subjective Evidence Evaluation Survey (SEES) to evaluate how each analysis team views the methodological appropriateness of the research design and the strength of evidence for the hypothesis. We illustrate the usefulness of the SEES in providing richer evidence assessment with pilot data from a previous multi-analyst study.
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| 21. |
- Zillich, Lea, et al.
(author)
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Biological aging markers in blood and brain tissue indicate age acceleration in alcohol use disorder
- 2024
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In: ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH. - : John Wiley & Sons. - 2993-7175. ; 48:2, s. 250-259
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Journal article (peer-reviewed)abstract
- BackgroundAlcohol use disorder (AUD) is associated with increased mortality and morbidity risk. A reason for this could be accelerated biological aging, which is strongly influenced by disease processes such as inflammation. As recent studies of AUD show changes in DNA methylation and gene expression in neuroinflammation-related pathways in the brain, biological aging represents a potentially important construct for understanding the adverse effects of substance use disorders. Epigenetic clocks have shown accelerated aging in blood samples from individuals with AUD. However, no systematic evaluation of biological age measures in AUD across different tissues and brain regions has been undertaken.MethodsAs markers of biological aging (BioAge markers), we assessed Levine's and Horvath's epigenetic clocks, DNA methylation telomere length (DNAmTL), telomere length (TL), and mitochondrial DNA copy number (mtDNAcn) in postmortem brain samples from Brodmann Area 9 (BA9), caudate nucleus, and ventral striatum (N = 63-94), and in whole blood samples (N = 179) of individuals with and without AUD. To evaluate the association between AUD status and BioAge markers, we performed linear regression analyses while adjusting for covariates.ResultsThe majority of BioAge markers were significantly associated with chronological age in all samples. Levine's epigenetic clock and DNAmTL were indicative of accelerated biological aging in AUD in BA9 and whole blood samples, while Horvath's showed the opposite effect in BA9. No significant association of AUD with TL and mtDNAcn was detected. Measured TL and DNAmTL showed only small correlations in blood and none in brain.ConclusionsThe present study is the first to simultaneously investigate epigenetic clocks, telomere length, and mtDNAcn in postmortem brain and whole blood samples in individuals with AUD. We found evidence for accelerated biological aging in AUD in blood and brain, as measured by Levine's epigenetic clock, and DNAmTL. Additional studies of different tissues from the same individuals are needed to draw valid conclusions about the congruence of biological aging in blood and brain.
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